The proposed research is based on the long-term observation by pathologists, radiologists and clinicians that hyaline cartilage is a unique connective tissue which lacks a capillary blood supply and is not, or only rarely, invaded by neoplasms. It therefore represents a unique system to study both normal invasion (capillary penetration) as well as neoplastic invasive processes. We were able to show that cartilage contains tissue derived, low molecular weight proteins that act as protease inhibitors. Collagenases released by both normal and neoplastic cells can be inhibited by one of these proteins. Potentially invasive cells such as tumor cells (human osteosarcoma or metastatic breast carcinoma cells) or endothelial cells but not fibroblasts and smooth muscle cells are inhibited in their proliferation in culture by a cartilage derived anti-invasion factor (AIF) which contains both the proliferation and the protease inhibitory activity(ies). The proposed research intends to study and biochemically identify this cartilage derived anti-invasion factor.